rs727502862

Variant names:

• chr17-44399142-C-G
• rs727502862
• NM_001002909.4:c.2935G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-44399142-C-G
• chr17-44399142-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001002909.4(GPATCH8):​c.2935G>C​(p.Ala979Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000055 in 1,455,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: GPATCH8 NM_001002909.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.94
• Publications: 2 publications found

Genes affected

GPATCH8 (HGNC:29066): (G-patch domain containing 8) The protein encoded by this gene contains an RNA-processing domain, a zinc finger domain, a lysine-rich region and a serine-rich region. A mutation in the serine-rich region of the protein is thought to be associated with hyperuricemia (PMID: 21594610). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4203552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPATCH8	NM_001002909.4	c.2935G>C	p.Ala979Pro	missense_variant	Exon 8 of 8	ENST00000591680.6	NP_001002909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPATCH8	ENST00000591680.6	c.2935G>C	p.Ala979Pro	missense_variant	Exon 8 of 8	2	NM_001002909.4	ENSP00000467556.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000550 AC: 8 AN: 1455798 Hom.: 0 Cov.: 31 AF XY: 0.00000690 AC XY: 5 AN XY: 724668

African (AFR) AF: 0.00 AC: 0 AN: 33362

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106704

Other (OTH) AF: 0.00 AC: 0 AN: 60190

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Nov 01, 2011

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.9
PrimateAI	Uncertain	0.61	T
Sift4G	Benign	0.29	T
Polyphen		0.98	D
Vest4		0.52
MutPred		0.20		Gain of glycosylation at A979 (P = 0.0264);
MVP		0.56
MPC		0.18
ClinPred		0.62	D
GERP RS		5.1
Varity_R		0.41
gMVP		0.36
Mutation Taster		=24/76	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs727502862; hg19: chr17-42476510;